Human Gene BLNK (ENST00000224337.10) from GENCODE V44
Description: Homo sapiens B cell linker (BLNK), transcript variant 1, mRNA. (from RefSeq NM_013314) RefSeq Summary (NM_013314): This gene encodes a cytoplasmic linker or adaptor protein that plays a critical role in B cell development. This protein bridges B cell receptor-associated kinase activation with downstream signaling pathways, thereby affecting various biological functions. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signaling effectors following B cell receptor activation. Mutations in this gene cause hypoglobulinemia and absent B cells, a disease in which the pro- to pre-B-cell transition is developmentally blocked. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]. Gencode Transcript: ENST00000224337.10 Gencode Gene: ENSG00000095585.18 Transcript (Including UTRs) Position: hg38 chr10:96,189,171-96,271,569 Size: 82,399 Total Exon Count: 17 Strand: - Coding Region Position: hg38 chr10:96,191,973-96,271,398 Size: 79,426 Coding Exon Count: 17
ID:BLNK_HUMAN DESCRIPTION: RecName: Full=B-cell linker protein; AltName: Full=B-cell adapter containing a SH2 domain protein; AltName: Full=B-cell adapter containing a Src homology 2 domain protein; AltName: Full=Cytoplasmic adapter protein; AltName: Full=Src homology 2 domain-containing leukocyte protein of 65 kDa; Short=SLP-65; FUNCTION: Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR- mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis. SUBUNIT: Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2. Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts with SCIMP. SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=BCR activation results in the translocation to membrane fraction. TISSUE SPECIFICITY: Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon. PTM: Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-96 facilitates BTK binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca(2+) and MAPK signaling pathways. DISEASE: Defects in BLNK are the cause of agammaglobulinemia type 4 (AGM4) [MIM:613502]. It is a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. SIMILARITY: Contains 1 SH2 domain. WEB RESOURCE: Name=BLNKbase; Note=BLNK mutation db; URL="http://bioinf.uta.fi/BLNKbase/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q8WV28
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK225546 - Homo sapiens mRNA for B-cell linker variant, clone: KDN02487. BC018906 - Homo sapiens B-cell linker, mRNA (cDNA clone MGC:10542 IMAGE:4053894), complete cds. BC110298 - Homo sapiens B-cell linker, mRNA (cDNA clone IMAGE:5213221). AF068180 - Homo sapiens B cell linker protein BLNK mRNA, alternatively spliced, complete cds. AF068181 - Homo sapiens B cell linker protein BLNK-s mRNA, alternatively spliced, complete cds. AK027779 - Homo sapiens cDNA FLJ14873 fis, clone PLACE1002685, highly similar to B-cell linker protein. KJ898723 - Synthetic construct Homo sapiens clone ccsbBroadEn_08117 BLNK gene, encodes complete protein. AM180327 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 5-8 and 16 variant. AM180328 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 6-17 variant. AM180329 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 5-17 variant. AM180330 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 8-17 variant. AM180331 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 6-16 variant. AM180332 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 8-16 variant. AM180333 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 4-5 variant. AM180334 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 5-6 variant. AM180335 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 4-6 variant. AM180336 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 16 variant with intron 15 and 16 insertion. AM180337 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 16 variant. AM180338 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), variant with splice site slippage and 5-bp intronic insertion between exons 3 and 4. AM180339 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 6 variant. AM180340 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 8-9 and 16 variant. AM180341 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3,7 and 16 variant. AM180342 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3 and 16 variant. AM180343 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3 variant. AM180344 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3-4 variant. AM180345 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3,8 and 9 variant. AM180346 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), variant missing exons 3, and 4 and 5' end of exon 5. JD562620 - Sequence 543644 from Patent EP1572962. JD299586 - Sequence 280610 from Patent EP1572962. JD120611 - Sequence 101635 from Patent EP1572962. DQ583108 - Homo sapiens piRNA piR-50220, complete sequence. JD066931 - Sequence 47955 from Patent EP1572962. JD176595 - Sequence 157619 from Patent EP1572962. JD363555 - Sequence 344579 from Patent EP1572962. JD305424 - Sequence 286448 from Patent EP1572962. JD083703 - Sequence 64727 from Patent EP1572962. JD126519 - Sequence 107543 from Patent EP1572962. JD445295 - Sequence 426319 from Patent EP1572962. JD534917 - Sequence 515941 from Patent EP1572962. JD155968 - Sequence 136992 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04662 - B cell receptor signaling pathway hsa05340 - Primary immunodeficiency
Reactome (by CSHL, EBI, and GO)
Protein Q8WV28 (Reactome details) participates in the following event(s):
R-HSA-912724 CBL binds B-cell linker protein R-HSA-983703 p-6Y-SYK phosphorylates BLNK (SLP65) R-HSA-1112666 BLNK (SLP-65) Signalosome hydrolyzes phosphatidyinositol bisphosphate forming diacylglycerol and inositol-1,4,5-trisphosphate R-HSA-912631 Regulation of signaling by CBL R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling R-HSA-983705 Signaling by the B Cell Receptor (BCR) R-HSA-449147 Signaling by Interleukins R-HSA-1280218 Adaptive Immune System R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168256 Immune System